17th Post-ASCO Meeting for Belgium and Luxembourg Genval, Saturday June 21th, 2014 Bench to bedside Jacques De Grève MD, PhD Medical Oncology, Oncologisch Centrum UZ Brussel 1 Topics • Immunotherapy – Immune checkpoint drugs – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk Stem cell pathways Armed antibodies • Avatars • Genetic cancer Slide 3 Presented By Lauren Harshman at 2014 ASCO Annual Meeting Tumor Infiltrating Lymphocytes (TIL) • Prognostic +++++ • Predictive for response to a. b. c. Chemotherapy (Denkert) A510 Targeted therapies (Loi) Immunotherapy • Existing but suppressed immune response to cancer can be enhanced – Cytokines – Immune checkpoint drugs (+/-) – Adoptive cell therapies R/ Basis for Immune therapy – Immune Escape CD8 Presented By Tanguy Seiwert at 2014 ASCO Annual Meeting Slide 10 Presented By Oliver Dorigo at 2014 ASCO Annual Meeting Slide 11 Presented By Oliver Dorigo at 2014 ASCO Annual Meeting MEDI4736: An Engineered Anti-PD-L1 Antibody<br /> AstraZeneca Presented By Jose Lutzky at 2014 ASCO Annual Meeting Dose-Expansion Study in Multiple Tumor Types<br /> N= 346 Presented By Neil Segal at 2014 ASCO Annual Meeting Emerging Clinical Activity in Multiple Tumors<br /> Presented By Neil Segal at 2014 ASCO Annual Meeting PD-L1 Immunohistochemistry<br />Case Study in NSCLC<br /> Presented By Neil Segal at 2014 ASCO Annual Meeting <br /> Presented By Neil Segal at 2014 ASCO Annual Meeting Emerging Clinical Activity in Multiple Tumors<br /> Presented By Neil Segal at 2014 ASCO Annual Meeting Response in Patient with Pancreatic Cancer<br /> Presented By Neil Segal at 2014 ASCO Annual Meeting Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558, ONO-4538) in patients with platinum-resistant ovarian cancer Presented By Junzo Hamanishi at 2014 ASCO Annual Meeting Slide 16 Presented By Oliver Dorigo at 2014 ASCO Annual Meeting A Responder with Serous adenoca : <br />Nivolumab 3mg/kg Presented By Junzo Hamanishi at 2014 ASCO Annual Meeting A Responder with Clear cell carcinoma :<br />Nivolumab 3mg/kg Presented By Junzo Hamanishi at 2014 ASCO Annual Meeting A Phase Ib Study of Pembrolizumab (MK-3475) in Patients with HPV-negative and HPV-positive Head & Neck Cancer Anti-PD1 MSD Presented By Tanguy Seiwert at 2014 ASCO Annual Meeting 40 % 61 % Efficacy: Waterfall Plot* 7/25 Presented By Tanguy Seiwert at 2014 ASCO Annual Meeting 11/25 Slide 19 Presented By Tanguy Seiwert at 2014 ASCO Annual Meeting Slide 20 Phase 3 planned 2014 Presented By Tanguy Seiwert at 2014 ASCO Annual Meeting Predictive biomarkers for efficacy of checkpoint inhibitors ? 1. Immune-infiltrate in the tumor 2. PD-L1 expression in the tumor – For PD1/PD-L1 inhibitors 3. Neoantigens – For anti-CTLA4 Mutational Load Correlates with Clinical Benefit Anti-CTLA4 Presented By Alexandra Snyder Charen at 2014 ASCO Annual Meeting Slide 9 Presented By Alexandra Snyder Charen at 2014 ASCO Annual Meeting Neoepitope Signature Associated with Benefit in Validation Set Presented By Alexandra Snyder Charen at 2014 ASCO Annual Meeting Combined checkpoint inhibition Mechanism of action Presented By Hans Hammers at 2014 ASCO Annual Meeting Slide 12 Presented By Padmanee Sharma at 2014 ASCO Annual Meeting Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC) Presented By Hans Hammers at 2014 ASCO Annual Meeting Maximum tumor burden change in baseline target lesions Presented By Hans Hammers at 2014 ASCO Annual Meeting 45 % RR Change from baseline in target > 36 weeks tumor burden Now in first-line phase III Independent of PD-L1 expression Presented By Hans Hammers at 2014 ASCO Annual Meeting Nivolumab + sunitinib or pazopanib 50% RR Ph I Nivolumab Plus Sunitinib: <br />Recapitulating Immunoediting Concept? Presented By Lauren Harshman at 2014 ASCO Annual Meeting “Oncologic Logic”:<br />Immunotherapy Combinations Presented By Primo Lara at 2014 ASCO Annual Meeting Topics • Immunotherapy – Immune checkpoint drugs – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk Stem cell pathways Armed antibodies • Avatars • Genetic cancer Small molecule TKI specific for T790M in EGFR mutant lung adenocarcinoma Next Gen EGFR TKIs: Mutant Specific Agents Emerge Presented By Thomas Lynch at 2014 ASCO Annual Meeting Best response in Phase 1 and early <br />Phase 2 expansion cohort patients CO-1686 Presented By Lecia Sequist at 2014 ASCO Annual Meeting CO-1686 Sum of target lesions over time Presented By Lecia Sequist at 2014 ASCO Annual Meeting Progression-free survival (K-M estimate) CO-1686 Presented By Lecia Sequist at 2014 ASCO Annual Meeting CO-1686 activity superior to erlotinib in PC-9 (EGFRdel19) front-line model Presented By Lecia Sequist at 2014 ASCO Annual Meeting Topics • Immunotherapy – Immune checkpoint drugs – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk Stem cell pathways Armed antibodies • Avatars • Genetic cancer Activation of MET Presented By Gerald Falchook at 2014 ASCO Annual Meeting MET Amplification and c-Met Protein Expression in Select Cancers Antibodies and small molecule TKI’s Presented By John Strickler at 2014 ASCO Annual Meeting AMG 337 Best tumor responses Presented By David Hong at 2014 ASCO Annual Meeting Response in 63-year-old male with GEJ cancer and MET amplification Presented By David Hong at 2014 ASCO Annual Meeting Response in 63-year-old male with GEJ cancer and MET amplification Now phase 2 in MET amplified Presented By David Hong at 2014 ASCO Annual Meeting <br /> ABT-700 Targets the c-Met Pathway Presented By John Strickler at 2014 ASCO Annual Meeting <br />Treatment Emergent Adverse Events (AEs) for ABT-700 Monotherapy Treated Patients (in ≥15% of patients) Presented By John Strickler at 2014 ASCO Annual Meeting Best Percent Change in Target Lesions Presented By John Strickler at 2014 ASCO Annual Meeting Best Percent Change in Target Lesions in Subjects with MET Amplified Tumors Presented By John Strickler at 2014 ASCO Annual Meeting Topics • Immunotherapy – Immune checkpoint drugs • Inhibitory • Activating – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk Stem cell pathways Armed antibodies • Avatars • Genetic cancer Slide 3 Presented By Michael Birrer at 2014 ASCO Annual Meeting Slide 4 Presented By Michael Birrer at 2014 ASCO Annual Meeting Clinical Activities of JNJ-42756493 in Patients with FGFR Aberration in Tumor Treated at ≥ 6mg Dose Presented By David Solit at 2014 ASCO Annual Meeting Topics • Immunotherapy – Immune checkpoint drugs – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk/Trk Stem cell pathways Armed antibodies • Avatars • Genetic cancer Trk Rearrangements in Human Malignancy Presented By David Solit at 2014 ASCO Annual Meeting RXDX-101: Next Generation Kinase Inhibitor Presented By David Solit at 2014 ASCO Annual Meeting Observed Clinical Responses in Each of TrkA, ROS1 and ALK Patients Presented By David Solit at 2014 ASCO Annual Meeting Topics • Immunotherapy – Immune checkpoint drugs – Adoptive cell therapies • Targeted therapies – – – – – – HER pathway MET pathway FGFR pathway Ros/alk Stem cell pathways Armed antibodies • Avatars • Genetic cancer • End of presentation Slide 21 Presented By Jeffrey Abrams at 2014 ASCO Annual Meeting Anti-NaPi2b Antibody-Drug Conjugate (ADC): DNIB0600A sodium-dependent phosphate transporter protein 2b overexpressed in serous and clear cellAnnual OVCA Presented By Jeffrey Abrams at 2014 ASCO Meeting Response to Treatment and Maximum Declines in Measureable Disease by IHC Score Presented By Jeffrey Abrams at 2014 ASCO Annual Meeting Ovatars: Using Patient-Derived Xenografts for Selecting Best Therapies Presented By Paul Haluska at 2014 ASCO Annual Meeting Engraftment & Tumor Diversity Presented By Paul Haluska at 2014 ASCO Annual Meeting Slide 9 Presented By Paul Haluska at 2014 ASCO Annual Meeting Slide 10 Presented By Paul Haluska at 2014 ASCO Annual Meeting Ovarian avatars recapitulate clinical complications of donor patient tumors Presented By Paul Haluska at 2014 ASCO Annual Meeting Avatar Predictive for Platinum Response Presented By Paul Haluska at 2014 ASCO Annual Meeting Slide 16 Presented By Paul Haluska at 2014 ASCO Annual Meeting MC1463- Avatar Trial Presented By Paul Haluska at 2014 ASCO Annual Meeting Conclusions 1. Immunotherapy: an explosion 2. Targeted therapies: focus on cancers with a genomically activated target needed 3. Avatars to be further implemented, will be needed in drug development and individual patient management 4. Hereditary cancer predisposition deserves MUCH more attention for reasons of prevention and therapy
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